Quyu Shengxin Decoction Alleviates DSS-Induced Ulcerative Colitis in Mice by Suppressing RIP1/RIP3/NLRP3 Signalling

Abstract

Purpose. To study the therapeutic effect of Quyu (QY) Shengxin (SX) decoction (QYSXD) in mice with dextran sulfate sodium- (DSS-) induced ulcerative colitis and to investigate the effects of QYSXD on the regulation of the receptor-interacting protein kinase 1 (RIP1)/receptor-interacting protein kinase 3 (RIP3)/nucleotide-binding oligomerization domain-like receptor family pyrin domain protein 3 (NLRP3) signaling pathway. Method. Thirty-six mice were randomly divided into the following 6 groups: the experimental group (QYSX group), the model group (DSS group), the positive control group (5-aminosalicylic acid (5-ASA) group), the control group, the first component group (QY group), and the second component group (SX group). Each group included 6 mice. Ulcerative colitis (UC) was induced in the mice by providing 3.5% DSS in drinking water. The mice were weighed every day to evaluate the disease activity index (DAI). After 7 days, the mice were sacrificed, and colonic tissues were obtained for colon length measurement. The morphological changes in the colon and the pathological scores of the mice in each group were observed by hematoxylin-eosin (HE) staining. The messenger ribonucleic acid (mRNA) and protein expression levels of RIP1, RIP3, dynamin-related protein 1 (Drp1), NLRP3, cysteinyl aspartate specific proteinase-1 (caspase-1), interleukin (IL)-1β, and IL-18 in the colon tissues of the mice in each group were detected and compared by real-time quantitative reverse transcription PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). The levels of RIP1, RIP3, NLRP3, IL-1β, and IL-8 in the colonic mucosa were detected by ELISA. Western blotting was used to compare the protein expression of Drp1, caspase-1, mitochondrial fission protein 1 (FIS1), and mitophagy-associated protein light chain 3a/b (LC3a/b) among groups. The levels of reactive oxygen species (ROS) in the colonic mucosal cells were compared by immunofluorescence. Results. Compared with those in the DSS group, the mice with DSS-induced colitis in the QYSX group exhibited clearly higher body weights ( P < 0.05 ) and DAI scores ( P < 0.05 ). The colon lengths of the mice in the QYSX group were longer than those in the DSS group ( P < 0.05 ), and the pathological score of the QYSX group was lower than that of the DSS group ( P < 0.05 ). The RIP1, RIP3, Drp1, IL-1β, IL-18, and caspase-1 mRNA levels in the QYSX, 5-ASA, SX, and QY groups were significantly lower than those in the DSS group ( P < 0.05 ), but there were no differences between the QYSX group and the 5-ASA group. The levels of RIP1, RIP3, NLRP3, IL-1β, and IL-18 in the QYSX group were lower than those in the DSS group ( P < 0.01 ). The levels of Drp1, caspase-1, FIS1, and LC3a/b in the QYSX group and the 5-ASA group were lower than those in the DSS group ( P < 0.05 ). The levels of ROS in the colonic mucosal cells in the QYSX, 5-ASA, and QY groups were lower than those in the DSS group ( P < 0.05 ). Conclusion. QYSXD has certain therapeutic effects on DSS-induced colitis in mice and may be as effective as 5-ASA. QY and SX decoctions also have certain effects on colitis; however, these decoctions are not as beneficial as QYSXD. QYSXD may ameliorate colitis by inhibiting the expression of RIP1/RIP3/NLRP3 pathway-related proteins and reversing mitochondrial dysfunction to control inflammation.

3,5-Dimethyl-8-methoxy-3,4-dihydro-1H-isochromen-6-ol Attenuates Ulcerative Colitis via Targeting NLRP3 in Mice

“…32,33 The numbers of NLRP3 inflammasome significantly increased in mice with UC. 34 Subsequently, the active caspase-1 initiates the conversion and the secretion of pro-inflammatory cytokines IL-18 and IL-1β. 25 IL-1β not only directly induces the expression of IL-2 but also recruits neutrophils to increase inflammatory response and release other pro-inflammatory cytokines and chemokines, such as IL-6 and TNF-α, to accelerate inflammation response of UC.…”

Efficiency of a novel thermosensitive enema in situ hydrogel carrying Periplaneta americana extracts for the treatment of ulcerative colitis

“…Previously, some studies reported that necroptosis was involved in promoting inflammation and damage to the intestinal epithelium cells ( Wu et al, 2019 ; Wu et al, 2021 ; Xiao et al, 2021 ). Necroptosis, also known as programmed necrosis, is characterized by cell swelling, mitochondrial dysfunction, plasma membrane permeabilization, and the release of cytoplasmic content into the extracellular space.…”

“…It was shown that RIP3 and MLKL were upregulated in the inflamed tissues of UC patients, and were positively correlated with the severity of UC ( Wu et al, 2019 ). The RIP1/RIP3/NLRP3 signaling pathway mediated necroinflammation is known to be involved in UC ( Wu et al, 2021 ).…”

Ameliorative effect of ginsenoside Rg1 on dextran sulfate sodium-induced colitis: involvement of intestinal barrier remodeling in mice

“…Moringa seed extract QYSXD can improve colitis /RIP3/NLRP3 pathway related proteins and reverse mitochondrial dysfunction to control inflammation by inhibiting the expression of RIP1 ( 28 ). In addition, a study has shown that Xianglian pills can inhibit inflammation and improve the intestinal epithelial barrier, and Quyu Shengxin Decoction can inhibit enteritis by inhibiting the expression of proteins related to the RIP1/RIP3/NLRP3 signaling pathway ( 29 ).…”